Pre-clinical animal models and clinical trials have demonstrated the inter-relationships between bacterial infections and onset of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplant (HCT). Pre-existing acute GVHD is one of the strongest predictors for development of chronic GVHD, the most common cause of mortality in survivors beyond two years after HCT. Inhibition, of T cell activation and GVHD prophylaxis approaches, have not significantly improved acute GVHD incidence and severity rates. We hypothesize that reducing or minimizing the impact of bacterial microbes in the post-engraftment phase with potent, well-tolerated antibacterials will reduce infections in immuno-compromised allogeneic HCT recipients and lower the likelihood that the infused graft will be more activated against the host and thereby reduce the severity of GVHD. Decreasing post-engraftment infections will reduce the release of pro-inflammatory cytokines/other mediators, lower acute GVHD and subsequently chronic GVHD, and contribute to better long- term treatment outcomes. Specific Aims are: 1. Determine if use of prophylactic antibacterial agents prevent infection in the post-engraftment phase of allogeneic HCT. We will utilize a randomized, double-blinded, placebo-controlled trial design to show if susceptible bacterial infections can be prevented or reduced using antibacterial prophylaxis (moxifloxacin) in the post-engraftment phase (up to 100 days) after allogeneic HCT. Secondary objectives include determination of cumulative incidence of non-relapse mortality, acute and chronic GVHD rates and determination of overall survival of each cohort. 2. Determine the incidence and the onset of antibiotic resistance in all breakthrough bacterial isolates obtained from patients receiving placebo versus moxifloxacin study drug. This effort will be critical to understanding whether selection and emergence of multi-drug-resistant bacteria could be a detrimental consequence of extended antibiotic prophylaxis. 3. Determine differences in genetic, transcriptional, and proteomic biomarkers in patients receiving placebo versus study drug. This objective prospectively will identify biomarkers, including candidate molecules such as IL-113, IL-6, IL-1 Ra, IL-10 and TNF-a and other markers of immune engraftment and GVHD that may predict for risk of infection after HCT. Biostatisticians will perform multivariate analyses to identify the link between laboratory marker and clinical events (immune-dysregulation with acute and chronic GVHD, regimen-related toxicity and overall outcome). This approach will lead to creation of a risk profile for infection and GVHD. We will employ companion protocols developed within the BMT CTN. RELEVANCE (See instrucfions): Hematologic malignancies will account for 137,260 new cases and 54,020 deaths in the United States in 2010. HCT has made a significant impact upon improving outcome in this patient population. Distinct and critical barriers to further advances in HCT are infection and GVHD. Our proposed investigations using prophylactic antibacterials have the potential to reduce bacterial infections and GVHD in the post-engraftment phase of allogeneic HCT.